DESCRIPTION (Adapted from applicant's description): This K08 award will allow the candidate to obtain the scientific expertise and to conduct studies that will advance understanding of the functions of selected placental peptidases. Specifically, she will test hypotheses about the mechanisms by which alterations in the enzymes that process and metabolize Endothelin-1 are related to the pathogenesis of pre-eclampsia and pre-term labor and by which alterations in the carboxypeptidases that process a variety of peptide hormones and growth restriction. Specific aim 1 will test the hypothesis that two closely related metalloendopeptidases, endothelin converting enzyme-1 (ECE-1) and neutral endopeptidase (NEP), function in the regulation of levels of endothelin-1 (ET-1) in the placenta and that ET-1 functions as a common pathway in the pathogenesis of pre-eclampsia and pre-term labor. Aim 2 will test the hypothesis that recently identified members of the carboxypeptidase E family, highly concentrated in the rat placenta, also function as peptide processing enzymes in the human placenta. Specific aim 3 will test the hypothesis that the novel placental proteins also have nonenzymatic functions.